Selective addition of CXCR3+CCR4-CD4+ Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro

다국어 초록 (Multilingual Abstract)

Increasing importance is being given to the stimulation
of Th1 response in cancer immunotherapy because its
presence can shift the direction of adaptive immune responses
toward protective immunity. Based on chemokine
receptor expression, CXCR3+CCR4-CD4+ T
cells as Th1-type cells were investigated its capacity
in monocyte-derived dendritic cell (DC) maturation
and polarization, and induction of antigen specific cytotoxic
T lymphocytes (CTL) in vitro. The levels of IL-4,
IL-5 and IL-10 were decreased to the basal level compared
with high production of IFN-γ, TNF-α, and IL-2 in
CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3
and anti-CD28 antibodies. Co-incubation of activated
CD4+ or CXCR3+CCR4-CD4+ T cells with DC (CD4+/DC
or CXCR3+CD4+/DC, respectively) particularly up-regulated
IL-12 and CD80 expression compared with DC
matured with TNF-α and LPS (mDC). Although there
was no significant difference between the effects of the
CXCR3+CCR4-CD4+ and CD4+ T cells on DC phenotype
expression, CXCR3+CD4+/DC in CTL culture were able
to expand number of CD8+ T cells and increased frequencies
of IFN-γ secreting cells and overall cytolytic
activity against tumor antigen WT-1. These results
demonstrated that the selective addition of CXCR3+
CCR4- CD4+ T cells to CTL cultures could enhance the
induction of CTLs by DC in vitro, and implicated on a
novel strategy for adoptive T cell therapy.

다국어 초록 (Multilingual Abstract)

Increasing importance is being given to the stimulation
of Th1 response in cancer immunotherapy because its
presence can shift the direction of adaptive immune responses
toward protective immunity. Based on chemokine
receptor expression, CXCR3+CCR4-CD4+ T
cells as Th1-type cells were investigated its capacity
in monocyte-derived dendritic cell (DC) maturation
and polarization, and induction of antigen specific cytotoxic
T lymphocytes (CTL) in vitro. The levels of IL-4,
IL-5 and IL-10 were decreased to the basal level compared
with high production of IFN-γ, TNF-α, and IL-2 in
CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3
and anti-CD28 antibodies. Co-incubation of activated
CD4+ or CXCR3+CCR4-CD4+ T cells with DC (CD4+/DC
or CXCR3+CD4+/DC, respectively) particularly up-regulated
IL-12 and CD80 expression compared with DC
matured with TNF-α and LPS (mDC). Although there
was no significant difference between the effects of the
CXCR3+CCR4-CD4+ and CD4+ T cells on DC phenotype
expression, CXCR3+CD4+/DC in CTL culture were able
to expand number of CD8+ T cells and increased frequencies
of IFN-γ secreting cells and overall cytolytic
activity against tumor antigen WT-1. These results
demonstrated that the selective addition of CXCR3+
CCR4- CD4+ T cells to CTL cultures could enhance the
induction of CTLs by DC in vitro, and implicated on a
novel strategy for adoptive T cell therapy.

참고문헌 (Reference)

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